Dataset Information

Trimester-Specific Blood Trihalomethane and Urinary Haloacetic Acid Concentrations and Adverse Birth Outcomes: Identifying Windows of Vulnerability during Pregnancy

ABSTRACT: Background: Some disinfection by-products (DBPs) are reproductive and developmental toxicants in laboratory animals. However, studies of trimester-specific DBP exposure on adverse birth outcomes in humans are inconsistent. Objective: We examined whether trimester-specific blood and urinary biomarkers of DBP were associated with small for gestational age (SGA), low birth weight (LBW), and preterm birth. Methods: A total of 4,086 blood and 3,951 urine samples were collected across pregnancy trimesters among 1,660 mothers from Xiaogan City, China. Blood samples were quantified for biomarkers of trihalomethanes (THMs): chloroform (TCM), bromodichloromethane, dibromochloromethane, and bromoform. Urine samples were quantified for biomarkers of haloacetic acids (HAA): dichloroacetic acid and trichloroacetic acid. Birth outcomes were abstracted at delivery from medical records. We used Poisson regression models with log link functions to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for SGA, LBW, and preterm birth across tertiles (or categories) of DBP biomarker concentrations measured across pregnancy trimesters. We also examined the relative exposure differences across gestation comparing adverse outcomes with normal births using mixed-effects models. Results: Blood TCM concentrations in the second trimester were associated with an elevated risk of SGA comparing middle vs. lowest (RR, 2.34; 95% CI: 1.02, 5.35) and highest vs. lowest (RR, 2.47; 95% CI: 1.09, 5.58) exposure groups. Third-trimester blood TCM concentrations were also associated with an increased risk of SGA comparing the second tertile with the first (RR, 2.61; 95% CI: 1.15, 5.92). We found that maternal blood TCM concentrations were significantly higher for SGA compared with non-SGA births across the period from 23 to 34 wk gestation. Other blood and urinary DBP biomarkers examined were unrelated to SGA, LBW, or preterm birth. Conclusion: Blood TCM concentrations in mid to late pregnancy were associated with an increased risk of SGA, whereas other biomarkers of DBPs examined across pregnancy were not associated with birth outcomes. https://doi.org/10.1289/EHP7195

SUBMITTER: Sun Y

PROVIDER: S-EPMC7539675 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background: The programming of innate and adaptive immunity plays a pivotal role in determining the course of pregnancy, leading to either normal term birth (TB) or preterm birth (PB) through the modulation of macrophage (M1/M2) differentiation. Extracellular vesicles (EVs) in maternal blood, harboring a repertoire of physiological and pathological messengers, are integral players in pregnancy outcomes. It is unknown whether urinary EVs (UEVs) could serve as a non-invasive mechanistic biomarker for predicting PB. Methods: This study investigated first-trimester UEVs carrying M1 messengers with altered immune programming, aiming to discern their correlation to subsequent PB. A birth cohort comprising 501 pregnant women, with 40 women experiencing PB matched to 40 women experiencing TB on the same day, was examined. First-trimester UEVs were isolated for the quantification of immune mediators. Additionally, we evaluated the UEV modulation of "trained immunity" on macrophage and lymphocyte differentiations, including mRNA expression profiles, and chromatin activation modification at histone 3 lysine 4 trimethylation (H3K4me3). Results: We found a significant elevation (p < 0.05) in the particles of UEVs bearing characteristic exosome markers (CD9/CD63/CD81/syntenin) during the first trimester of pregnancy compared to non-pregnant samples. Furthermore, UEVs from PB demonstrated significantly heightened levels of MCP-1 (p = 0.003), IL-6 (p = 0.041), IL-17A (p = 0.007), IP-10 (p = 0.036), TNFα (p = 0.004), IL-12 (p = 0.045), and IFNγ (p = 0.030) relative to those from TB, indicative of altered M1 and Th17 differentiation. Notably, MCP-1 (>174 pg/mL) exhibited a sensitivity of 71.9% and specificity of 64.6%, and MCP-1 (>174 pg/mL) and IFNγ (>8.7 pg/mL) provided a higher sensitivity (84.6%) of predicting PB and moderate specificity of 66.7%. Subsequent investigations showed that UEVs from TB exerted a significant suppression of M1 differentiation (iNOS expression) and Th17 differentiation (RORrT expression) compared to those of PB. Conversely, UEVs derived from PB induced a significantly higher expression of chromatin modification at H3K4me3 with higher production of IL-8 and TNFα cytokines (p < 0.001). Implications: This pioneering study provides critical evidence for the early detection of altered M1 and Th17 responses within UEVs as a predictor of PB and early modulation of altered M1 and Th17 polarization associated with better T-cell regulatory differentiation as a potential prevention of subsequent PB.

Dataset Information

Trimester-Specific Blood Trihalomethane and Urinary Haloacetic Acid Concentrations and Adverse Birth Outcomes: Identifying Windows of Vulnerability during Pregnancy

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets